- Homozygous for uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele * All patients will be tested for UGT1A genotype prior to starting treatment and be excluded if they are homozygous for the UGT1A1*28 allele (UGT1A1 7/7 genotype); irinotecan's active metabolite glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) is inactivated through glucuronidation by uridine diphosphate glucuronosyltransferases (UGTs) mainly in the liver and is excreted through the bile ducts; a meta-analysis demonstrated that the UGT1A1*28 genotype is moderately predictive of severe irinotecan induced hematologic toxicity at moderate doses and strongly predictive at high doses, and in 2005, the Food and Drug Administration (FDA) added a warning to the irinotecan packaging label that patients with the UGT1A1*28 genotype were at increased risk for neutropenia